16-4512469-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013399.3(CDIP1):c.*103C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 827,240 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (5 hom.)
• Consequence: CDIP1 NM_013399.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

Genes affected

CDIP1 (HGNC:13234): (cell death inducing p53 target 1) Predicted to enable metal ion binding activity. Acts upstream of or within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and tumor necrosis factor-mediated signaling pathway. Located in cytoplasmic side of late endosome membrane; cytoplasmic side of lysosomal membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-4512469-G-A is Benign according to our data. Variant chr16-4512469-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDIP1	NM_013399.3	c.*103C>T		3_prime_UTR_variant	6/6	ENST00000567695.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDIP1	ENST00000567695.6	c.*103C>T		3_prime_UTR_variant	6/6	1	NM_013399.3	P1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 559 AN: 152138 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00391 AC: 656 AN: 167692 Hom.: 2 AF XY: 0.00405 AC XY: 366 AN XY: 90312

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00326

Gnomad ASJ exome AF: 0.00450

Gnomad EAS exome AF: 0.0000805

Gnomad SAS exome AF: 0.00132

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.00503

GnomAD4 exome AF: 0.00455 AC: 3073 AN: 674984 Hom.: 5 Cov.: 9 AF XY: 0.00444 AC XY: 1576 AN XY: 355346

Gnomad4 AFR exome AF: 0.00110

Gnomad4 AMR exome AF: 0.00374

Gnomad4 ASJ exome AF: 0.00490

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00132

Gnomad4 FIN exome AF: 0.00512

Gnomad4 NFE exome AF: 0.00557

Gnomad4 OTH exome AF: 0.00454

GnomAD4 genome AF: 0.00367 AC: 559 AN: 152256 Hom.: 2 Cov.: 33 AF XY: 0.00330 AC XY: 246 AN XY: 74438

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00528

Gnomad4 NFE AF: 0.00523

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00426 Hom.: 0

Bravo AF: 0.00347

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CDIP1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.28
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1861653; hg19: chr16-4562470;